Depression Risk Factors With HIV -- Plus Screening and Diagnosis Keys

Abstract: Independent risk factors for depression in people with HIV infection can be grouped into sociodemographic variables (including female gender, unemployment, and financial difficulties), behavioral factors (including injection drug use and other substance use and abuse), clinical factors (including less antiretroviral experience, poor antiretroviral adherence, and a detectable viral load), and psychological factors (including a family or personal history of depression and low self-efficacy). Research throughout the Western world shows that depression often goes undiagnosed and untreated in HIV-positive people. HIV health experts in the United States and Europe recommend screening everyone with HIV for depression. European AIDS Clinical Society (EACS) guidelines offer straightforward advice on screening for and diagnosing depression in people with HIV.

Why is depression so prevalent in people with HIV infection? One inescapable reason is that depression ranks high among risk factors for HIV infection, so depression often precedes HIV infection and the two coexist after seroconversion. Depression goes hand-in-hand with behaviors that boost HIV risk, such as injecting drugs, abusing alcohol and other substances,1 and frequent sex without condoms. The link between depression and HIV risk also holds true in people without a substance abuse history. One study from the first decade of the US HIV epidemic charted a 7-fold higher rate of lifetime mood disorders in nonabusers seeking HIV testing than in the general population.2

Thus any survey of depression risk in people with HIV must be read with the understanding that relevant research rarely establishes causality. But a grasp of which variables hold the strongest associations with depression in HIV populations can be a crucial step toward heightened awareness of depression in people with HIV -- and toward possible diagnosis and treatment.

Depression Risk Factors Fit in Four Bins

European AIDS Clinical Society (EACS) guideline writers believe depression poses such a threat to people with HIV that everyone infected should be screened for depression immediately after HIV diagnosis and every 1 to 2 years thereafter (see "Screening and Diagnosis Simplified" below).3 These guidelines offer a 7-point framework as a starting point for identifying HIV-positive people at high risk for depression:

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Family history of depression

Personal history of depressive episode

Older age

Adolescence

History of drug addiction or psychiatric, neurologic, or severe somatic comorbidity

Efavirenz use

Use of neurotropic or recreational drugs

Specific depressive symptoms in men may include feeling stressed or burned out, venting feelings in angry outbursts, and coping through overwork and heavy drinking.3 But this list is hardly immutable. For example, some HIV research shows a diminishing risk of depression with age,4-6 and research does not consistently confirm a link between efavirenz and depression.7

Analysis of 11 studies from the combination antiretroviral era (Table 1)4-14 suggests several other variables independently associated with depression that fit into four broad bins: (1) sociodemographic, (2) behavioral, (3) clinical, and (4) psychological (Table 2). The research explored includes three prospective and eight cross-sectional studies involving 15,480 people with HIV infection. Six studies came from the United States (n = 4766), two from Denmark (n = 417), and one each from Switzerland (n = 4422), Spain (n = 5185), and Italy (n = 690) (Table 1). Participants in most of these 11 studies averaged about 40 years in age except for one study of people 50 or older10 and one study of US youth.14 About half of participants in the study of US youngsters were female,14 while women made up one quarter to one third of the other study groups.

Other psychological problems (loneliness,10 dissatisfaction with current life,13 self-reported stress13)

Low self-efficacy (belief in one's ability to accomplish things)8,9

Constant thoughts about HIV,5 perception that HIV affects all aspects of life13

Among sociodemographic factors, certain variables consistently predict depression from study to study: female gender, homosexual orientation, living alone, and unemployment or low income (Table 2). Three studies found a consistent association between female gender and higher depression risk,4,8,12 though some experts question the strength of this link on the grounds that men are less likely than women to admit depressive symptoms on testing. Living without a spouse or partner boosted depression risk in the Swiss HIV Cohort Study4 and made suicidal ideation more likely in a 4-city US study.9 Unemployment or limited ability to work got tied to depression in the United States,6 Italy,12 and Switzerland.4 A single-center study in St. Louis, Missouri found that having one or more minor dependents (versus none) made depression more likely.6 Financial straits5,8 or low access to medical care8 contributed to depression in Houston8 and Denmark.5 Homosexual versus heterosexual orientation made depression5 or suicidal ideation9 more likely in Denmark or 4 US cities. In a study of 186 HIV-positive youngsters at five US sites, those behaviorally infected rather than perinatally infected ran a higher risk of depression.14

Analysis of these studies yields no tidy take-home on how age affects depression risk. The study of HIV-positive US youth found depression more likely in older youngsters,14 while a study of US HIV patients 50 or older found depression more likely in younger cohort members.10 A 4422-person Swiss HIV Cohort Study analysis found incident depression more frequent in people under 45 (versus over 55), while cumulative prevalent depression proved more frequent in people over 45 (versus under 45).4 Studies of middle-aged adults in St. Louis6 and Denmark5 found depression more likely in younger study participants. A comparison of HIV-positive and negative US veterans at five sites determined that depressive symptom frequency dropped with age in HIV-negative vets but not HIV-positive vets.11 Depression prevalence rose with age in veterans with HIV compared with HIV-negative veterans. The message from this drove of data may be to consider age a less reliable depression predictor than other factors.

Among behavioral factors tied to depression, injection drug use looms large. In the Swiss HIV Cohort Study, men who inject drugs ran a higher risk of incident depression and cumulative prevalent depression than white men who have sex with men (MSM), while women who inject drugs had a higher risk of cumulative prevalent depression.4 Research elsewhere in Europe and the United States also confirms illicit drug use,12 recent substance abuse,8 regular marijuana use,9 previous alcohol abuse,13 and smoking12 as depression risk factors. In the Swiss study, lack of physical activity boosted chances of incident or prevalent depression, and sexually active people ran higher risks of both incident and prevalent depression.4 The study of US youth found an unsurprising link between more behavioral problems and depression.14

These 11 US and European studies turned up several links between antiretroviral therapy, its benefits, and depression. In a 5185-person Spanish cohort, both starting ART and longer ART exposure (including longer efavirenz use) lowered the risk of clinically significant depression.7 Lower nadir CD4 count heightened risk of incident depression in Switzerland,4 while a pre-ART CD4 count below 200 cells/mm3 raised depression risk in a US study.8 Having a detectable viral load made depression more likely in Switzerland4 and the United States.6 Two studies in Denmark linked poor antiretroviral adherence to depression.5,13 Other clinical variables tied to depression or suicidal ideation include worse HIV symptom severity,9 decreased cognitive function,10 cirrhosis,12 self-reported poor health,13 and reduced energy.10

A previous depression diagnosis raised odds of a new episode almost 10-fold in the Italian cohort.12 Related variables that made depression more likely include previously seeking help for psychological problems;13 guilt, shame, stigma, or leading a double life with HIV;5,10,14 low self-efficacy (belief in one's ability to accomplish things);8,9 increased loneliness;10 dissatisfaction with one's current life;13 self-reported stress;13 constant thoughts about HIV;5 and the perception that HIV affects all aspects of life.13

Table 2 outlines the risk factors summarized in the preceding paragraphs, creating a checklist clinicians can use when evaluating a patient for depression.

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